Mechanisms of Vascular Defects in Diabetes Mellitus

This book comprising 24 chapters is devoted to the mechanisms for the pathogenesis of the spectrum of vascular diseases in diabetes. Cellular events and molecular pathways that regulate the structure and function of both small and large arteries, the dysregulation in these vessels caused by hyperglycemia, oxidative stress, metabolic and haemostatic derangements secondary to diabetes, are discussed. Mechanisms of vascular remodelling and rupture of atherosclerotic plaques in diabetes are also covered. Several of the reviews also discuss therapeutic targets and drugs employed to reduce endothelial dysfunction and vascular inflammation in diabetes. All articles are authored by experts in their respective research fields.

This compendium will be of interest to both basic scientists and clinicians in the pursuit of unravelling the molecular basis of vascular diseases and also to those who seek to identify targets for therapy of vascular complications of diabetes.

Auteur

Dr. Chandrasekharan C. Kartha is an Honorary Distinguished Professor in the Division of Cardiovascular Diseases and Diabetes Biology at Rajiv Gandhi Center for Biotechnology at Thiruvananthapuram, India. He is a pathologist by training and has made significant contributions to the understanding of the cellular and molecular mechanisms of vascular diseases and endomyocardial fibrosis, a tropical cardiomyopathy. He is an elected fellow of Royal College of Physicians (London), International Academy of Cardiovascular Sciences, National Academy of Medical Sciences (India) National Academy of Sciences (India) and Indian Academy of sciences. He has served on the editorial boards of several journals and in grant review committees of several India government agencies funding medical research and science and technology activities. He has organized several national and international conferences on cardiovascular themes and has been an invited speaker at several national andinternational meetings. He has published more than 120 papers in refereed journals, 15 chapters in books and edited 5 books. He is the current President of Academy of Cardiovascular Sciences, the India section of International Academy of Cardiovascular Sciences.

Résumé
This book intends to bring together, a panel of renowned experts in the field of vascular biology and diabetology, to integrate the current understanding of the pathogenesis and pathophysiology of vascular diseases in diabetes mellitus. This attempt is significant given the increasing interest in this area as the prevalence of vascular diseases continues to escalate globally. Patients with diabetes are at a higher risk of structural and functional changes in all vessel walls of the human body. Vascular complications of diabetes are leading causes for both morbidity and mortality.
In recent years, several articles have focused on advancing our knowledge on the profound effect of hyperglycemia and insulin resistance on building up vascular wall inflammation leading to endothelial dysfunction in patients with diabetes mellitus Other reports have elaborated on the various disorders, hyperglycemia can lead to, their therapies, adverse effects and complications. There are also studies that highlight the role of factors that induce vascular wall alterations in hyperglycemia.
In this book, we attempt to discuss vascular disease progression in diabetes with a unique approach. We attempt to provide a complete perspective of the pathophysiology of vascular complications and then dissect each of the factors that play a key role in accelerating vascular wall alterations in diabetes. Each of these factors has been adversely implicated in the initiation and progression of disease to a large extent. In this collection for the first time all these factors would be described under a common canopy. Further, the text would emphasize on pathogenesis of micro vascular complications of diabetes, such as retinopathy, neuropathy and nephropathy. Pharmacological therapies for treating vascular dysfunction in diabetes mellitus would also be reviewed. This compendium hopefully would be an invaluable replacement to scores of literature on diabetic vascular disease and would be of great interest to clinicians, academicians, medical students and researchers.
The book will be divided into seven sections, each emphasizing a common incentive to development of vascular disease in diabetes. Section I deals with pathophysiology of diabetic vascular disease, beginning with an update on the global burden of diabetes mellitus and its vascular complications. The pathophysiology and pathogenesis of diabetes associated macrovasculopathy, how hyperglycemia functions as an atherogenic factor, effects of hyperglycemia on smooth muscle accumulation in vascular lesions and genetic susceptibility for increased risk of vascular disease in diabetes will be discussed in the following chapters of this section.
The next section (Section II) surveys the process of endothelial dysfunction under hyperglycaemia and hyperinsulinemia and their effects on angiogenesis, vascular remodeling and wound healing. A chapter is also dedicated to the endothelial progenitor cell population and its dysfunction during development of vascular complications in diabetes.
Section III will highlight the molecular mechanisms underlying endothelial dysfunction, various pathways such as nitric oxide synthase pathway, oxidative stress pathway, renin angiotensin system and increased vascular superoxide production in the initiation and progression of vascular disease in diabetes. This section also covers role of endothelin, monocyte derived cytokines, peroxynitrate and adipokines in macrovascular complications of diabetes.
Metabolic factors such as advanced glycation end products, atherogenic dyslipoproteinaemia, and homocysteine will be reviewed in Section IV, whereas an overview of the hemostatic factors such as platelet dysfunction, hyperglycaemia induced thrombin formation and aberrant clot lysis will be dwelled upon in Section V.Section VI includes chapters on microvascular complications of diabetes which encompasses long term complications of diabetes affecting small blood vessels of the eye, kidneys and nervous system. The pathogenesis and mechanisms of these complications would be detailed here.
The final section (Section VII) of the book will consider mechanism of action of drugs for treating endothelial dysfunction in diabetes mellitus which would elaborate on lipid regulating therapies such as statins, as well as other therapies such as ACE inhibitors, Angiotensin II receptors, insulin, metformin and their effects on enhancing vascular function in diabetes.We intend to invite authors who symbolize a multidiscipli...

Contenu

Section 1 Introduction.- The Global Burden Of Diabetes And Its Vascular Complications.- SECTION 2 Pathogenesis.- Genetic Basis For Increased Risk For Vascular Diseases In Diabetes.- Vascular Remodelling In Diabetes Mellitus.- Pathogenesis Of The Plaque Vulnerability In Diabetes Mellitus.- Endothelial Dysfunction In Diabetes.- Smooth Muscle Cells In Diabetes Mellitus.- Monocytes Factors In Pathogenesis Of Vascular Lesions In Diabetes.- Endothelial Progenitor Cell Dysfunction In The Pathogenesis Of Vascular Complications Of Diabetes.- Pathogenetic mechanisms in diabetic retinopathy: from molecules to cells to tissues.- Perspectives on the vascular pathogenesis of diabetic neuropathy.- SECTION 3 Molecular mechanisms.- The Renin - Angiotensin System And Diabetes.- Adipokines And Vascular Disease In Diabetes.- G-Proteins In Vascular Complications Of Diabetes.- Histone Deacetylases In Vascular Pathophysiology: Regulation By Vasoactive Peptides And Growth Factors.- Role of non-coding RNAs in vascular complications of diabetes mellitus.- SECTION 4 Hemostatic Factors.- Diabetes As A Prothrombotic State.- Mechanisms Of Hypercoagulation And Aberr…